MXPA01002687A

MXPA01002687A - Process for preparing resorcinol derivatives

Info

Publication number: MXPA01002687A
Application number: MXPA/A/2001/002687A
Authority: MX
Inventors: Kitchin John; Edward Bradley Stuart; Michael Wynne Graham
Original assignee: Pfizer Products Inc
Priority date: 2000-03-15
Filing date: 2001-03-14
Publication date: 2002-06-05

Abstract

The present invention relates to an improved process for preparing 4-substituted resorcinol derivatives, and intermediate compounds useful in the preparation of such resorcinol derivatives.

Description

PROCESS FOR THE PREPARATION OF RESORCINQL DERIVATIVES FIELD OF THE INVENTION The present invention relates to an improved process for preparing 4-substituted resorcinol derivatives.

BACKGROUND OF THE INVENTION It is known that resorcinol derivatives are useful for a variety of purposes. For example, in the field of cosmetics, resorcinol derivatives have been used as agents for lightening the skin. The use of resorcinol derivatives as skin lightening agents is described in European patent application EP 907,774, published on March 31, 1999; the patent of E.U.A. No. 5,468,472, granted on November 21, 1995; the patent of E.U.A. No. 5,399,785, granted on March 21, 1995; European patent application EP 623,339, published on November 9, 1994; JP 5-4905, published on January 14, 1993, and European patent application EP 341, 664, published on November 15, 1989. Resorcinol derivatives have also been used as agents to control dandruff (document JP 4-169516, published June 17, 1992); as anti-acne agents (JP 4-169511, published June 17, 1992); as enhancers of antimicrobial compounds (U.S. Patent No. 4,474,748, issued October 2, 1984); as agents to prevent the appearance of brown color in foods (U.S. Patent No. 5,304,679, issued April 19, 1994); and the preparation of photographic dye images (U.S. Patent No. 3,756,818, issued September 4, 1973). The present invention provides an improved process for preparing 4-substituted resorcinol derivatives. The present invention further provides useful intermediate compounds for preparing these resorcinol derivatives, as well as processes for preparing intermediate compounds. The improved process of the present invention is easier to use than conventional methods for preparing resorcinol derivatives in large quantities. In addition, the improved process of the present invention results in a higher yield of the final product than conventional methods.

BRIEF DESCRIPTION OF THE INVENTION The invention provides a process for preparing a resorcinol derivative of formula I: or its pharmaceutically acceptable salt, wherein the broken line indicates an optional double bond at that position, and wherein X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C2) alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C4-C8) cycloalkyl ring or a cycloalkenyl ring (Cs-Cs), with the proviso that the ring cycloalkyl (C4-C8) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and the alkyl (CrC2), alkenyl (C2-C12), alkynyl (C2-C2), the cycloalkyl ring (Gt-Cs) or the cycloalkenyl ring (Cs-Cß) are optionally substituted with one to three groups Z independently selected, and Z is any substituent capable of being substituted therein, and the process of the present invention can be used to prepare the particular substituted resorcinol derivative. In a preferred embodiment, Z is selected from the group consisting of cyano; halo; alkyl (C-i-Ce); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-C9); aryl (C6 alkyl) -; = O; = CHO (C? -C6 alkyl); Not me; hydroxy, alkoxy (CrC6); aryl (C6-C6 alkoxy) -; acyl (C? -C6); alkylamino (d-C6) -; aryl (C 1 -C 6 alkylamino) -; aminoalkyl (d-C6) -; alkoxy (CrC6) -CO-NH; alkylamino (C? -C6) -CO-; alkenyl (C2-C6), alkynyl (C2-C6), hydroxyalkyl (d-Ce) -; (C6-C6 alkoxy) (C6-C6 alkyl) -; (acyloxy d-Cß) (d-Cß alkyl) -; nitro; cyanoalkyl (d-Cß) -; haloalkyl (d-Cß) -; nitroalkyl (C Cd) -; trifluoromethyl; trifluoromethyl (d-Cß alkyl) -; acylamino (d-Cß) -; (acylamino d-Cß) (alkyl CI-CT) -; (alkoxy d-Cß) (acylamino d-Cß) -; aminoacyl (d-Cß) -; (aminoacyl dCe) (dCS alkyl) -; (alkylamino d-Cß) (acyl d-Cß) -; (C 1 -C 6 alkyl) 2-aminoacyl (d-Cß) -; -CO2R2; -alkyl (d-C6) -C02R 2; -C (0) N (R2) 2; -alkyl (C? -C6) -C (O) N (R2) 2; R2ON =; R2ON = alkyl (d-C6) -; R2ON = CR2 (alkyl dC6) -; -NR2 (OR2); -alkyl (C C6) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (C? -C6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (d-Cß), aryl or aryl (C? -C6 alkyl) -; R3C (0) 0-, and R3 is (d-C6) alkyl, aryl or aryl (d-C6 alkyl) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (Ci-Ce alkyl) -; R 3 C (0) 0-alkyl (C? -C6) -; R R5N-C (0) -0-; R4-R5NS (0) 2- R4R5NS (0) 2 (C6 alkyl) -; R S (0) 2R5N-; R 4 S (0) 2 R 5 N (C 6 alkyl) -; and m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (d-Cß); -C (= NR6) (N (R4) 2); -alkyl (d-C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (CI-CT alkyl); -NH (C1-C6 alkyl); aryl (alkyl d-CβJ-HN-; and a ketal) The present invention also provides various intermediates useful in this process, and methods for their preparation.Specifically, this invention relates to a process for preparing a compound of formula 6) (6) wherein W is hydrogen or a protecting group; and X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C2) alkynyl, or X and Y are taken together with the carbon to which they are attached to forming a cycloalkyl ring (d-Cß) or a cycloalkenyl ring (Cs-Cß), with the proviso that the cycloalkyl ring (d-Cß) or the cycloalkenyl ring (Cs-Cß) are not aromatic; and the alkyl (CC? 2), alkenyl (C2-C? 2), alkynyl (C2-Ci2), the cycloalkyl ring (d-Cß) or the cycloalkenyl ring (Cs-Cß) are optionally further substituted with one to three Z groups independently selected, and Z is as defined above; which comprises reacting a compound of formula (5) wherein Q is halogen, with a base to form the compound of formula (6). In a preferred embodiment, Q is bromine, iodine or chlorine; more preferably, Q is bromine or iodine; and most preferably, Q is bromine.

The present invention further provides a process for preparing a compound of formula (7) (7) wherein W, X and Y are as defined above; which comprises reacting a compound of formula (5) (5) wherein Q is as defined above, with a base to form the compound of formula (7).

In a preferred embodiment, the compound of formula (5) is prepared by reacting the compound of formula (4) (4) wherein W, X and Y are as defined above, with a halogenating agent, and the halogen corresponds to Q in the compound of formula (5). In a preferred embodiment, Q is bromine, and the compound of formula (5) is prepared by reacting the compound of formula (4) with a brominating agent, such as, for example, N-bromosuccinimide. In another preferred embodiment, the compound of formula (4) is prepared by reacting a compound of formula (2) (2) with a compound of formula (3) (3) wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).

The present invention further provides a process for preparing a compound of formula (5) (5) wherein Q, W, X and Y are as defined above, which comprises reacting the compound of formula (4) (4) with a halogenating agent, as described above, to form the compound of formula (5). In a preferred embodiment, the compound of formula (4) is prepared by reacting a compound of formula (2) (2) with a compound of formula (3) (3) wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4). The present invention further provides a process for preparing a compound of formula (4) (4) in which W, X and Y are as defined above; which comprises reacting a compound of formula (2) (2) with a compound of formula (3) (3) in the presence of a base to form the compound of formula (4). The present invention further provides a process for preparing a compound of formula I (a) the) wherein X and Y are as defined above, comprising: (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6); Y (6) (b) when W is H, reducing the compound of formula (6) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, reduce the compound of formula (6) formed in this manner and removing the protecting group, to form the compound of formula I (a). In a preferred embodiment, the compound of formula (6) is reduced to form the compound of formula I (a) by reaction with triethylsilane in the presence of a Lewis acid, or alternatively by hydrogenation under conventional conditions.

The present invention further provides a process for preparing a compound of formula I (a) l (a) in which X and Y are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (7), and (7) (b) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, hydrogenating the compound of formula (7) formed in this manner and removing the protecting group, to form the compound of formula I (a). The present invention further provides a process for preparing a compound of formula I (a) l (a) in which X and Y are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6); (6) (b) reacting the compound of formula (6) formed in this manner with a base, to form a compound of formula (7); Y (7) (c) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, hydrogenating the compound of formula (7) formed in this manner and removing the protecting group, to form the compound of formula I (a). The present invention further provides a process for preparing a compound of formula I (a) l (a) in which X and Y are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6); (6) (b) reacting the compound of formula (6) formed in this manner with a base, to form a compound of formula (7); and (7) (c) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, removing the protecting group of the compound (7) formed in this manner, to form the compound of formula I (b) Kb) and hydrogenate the compound of formula I (b) formed in this manner, to form the compound of formula I (a). The present invention further provides a process for preparing a compound of formula I (a) | (a) in which X and Y are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (7); Y (7) (b) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, remove the protecting group of the compound (7) formed in this manner, to form the compound of Formula I (b) l (b) and hydrogenating the compound of formula I (b) formed in this manner, to form the compound of formula I (a).

The present invention also comprises a process for prepare a compound of formula I (b) l (b) wherein X and Y are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6); (6) (b) reacting the compound of formula (6) formed in this manner with a base, to form a compound of formula I (b), when W is H, and a compound of formula (7) when W is a protective group; Y (7) (c) when W is a protecting group, remove the protecting group of the compound (7) formed in this manner, to form the compound of formula I (b). The present invention further provides a process for preparing a compound of formula I (b) Kb) in which X and Y barnidipine hydrochloride are as defined above, comprising; (a) reacting a compound of formula (5) (5) wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula I (b) when W is H, and a compound of formula (7) when W is a protective group; (7) (b) when W is a protecting group, remove the protecting group of the compound (7) formed in this manner, to form the compound of formula I (b). As explained below in the description of scheme 1, in which W is H, the compound of formula (5) can exist in equilibrium with the compound of formula (5 ') as follows: wherein W is H, and the compound of formula (5 ') can be formed directly from the compound of formula (4). In all the processes described herein in which W is H and the compound of claim (5) is used, the compound of claim (5 ') can be used in its place under the same reaction conditions indicated, for example , to prepare the compounds of formula (6) or (7). The present invention also provides a process for preparing the compound of formula (5 ') by treating the compound of formula (4), wherein W is H, with a halogenating agent to form the compound of formula (5'). The various processes of the present invention, as described above, are incorporated in scheme 1, which appears below. In a preferred non-limiting embodiment, X and Y are taken together with the carbon to which they are attached to form a cycloalkyl ring (Cs-Cß) or a cycloalkenyl ring (Cs-Cs), which has the following structure: wherein n is 0, 1, 2 or 3, and said cycloalkyl ring (Cs-Cs) or cycloalkenyl ring (Cs-Cß) are optionally substituted, and the dotted line indicates an optional double bond at that position. In a non-limiting embodiment, the cycloalkyl ring (C5-C8) or the cycloalkenyl ring (C5-Cs) are substituted with one to three independently selected Z groups, as defined above.

In a preferred embodiment, X and X are taken together with the carbon to which they are attached to form a cyclohexyl or cyclohexenyl ring, and more preferably a cyclohexyl ring. In another preferred embodiment, X and Y are taken together with the carbon to which they are attached to form a cyclopentyl or cyclopentenyl ring, and more preferably a cyclopentyl ring. In another preferred embodiment, the cycloalkyl ring (Cs-Cs) or the cycloalkenyl ring (Cs-Cs) are not substituted. In another preferred embodiment, the cycloalkyl ring (Cs-Cß) or the cycloalkenyl ring (Cs-Cs) are monosubstituted. More preferably, X and Y are taken together with the carbon to which they are attached to form a monosubstituted cyclohexyl ring or monosubstituted cyclopentyl. In another preferred embodiment, the cycloalkyl ring (Cs-Cs) or the cycloalkenyl ring (Cs-Cs) are disubstituted. More preferably, X and Y are taken together with the carbon to which they are attached to form a disubstituted cyclohexyl ring or disubstituted cyclopentyl. When X and Y are taken together with the carbon to which they are attached to form a cyclohexyl or cyclohexenyl ring, the ring is preferably substituted at the 3 or 4 position, and more preferably at the 4 position. When X and Y are taken together with the carbon to which they are attached to form a cyclopentyl or cyclopentenyl ring, the ring is preferably substituted at the 3-position.

In another preferred embodiment, X and Y are taken together with the carbon to which they are attached to form: n which is substituted with one to three independently selected Z groups, as defined above; wherein n is 0, 1 or 2. In another preferred embodiment, n is 0 or 1. In another preferred embodiment, n is 0; and the dashed line represents a double bond in that position. In another embodiment, n is 1. In another preferred embodiment, the ring formed by X and Y taken together with the carbon to which they are attached is substituted with OH, = 0, = NOH, CH2OH or or their combinations. In another preferred embodiment, n is 0; the ring formed by X and Y taken together with the carbon to which they are attached is substituted with = NOH; and the dashed line represents a double bond in that position.

In another preferred embodiment, n is 1; and the ring formed by X and Y taken together with the carbon to which they are attached, is substituted with OH, = 0, = NOH, CH2OH or OH < Me or their combinations. When Z is a heterocycloalkyl (C2-C9) substituent, it is preferably a group of the formula: where m is 0, 1 or 2, and Q is CH2, NR2, O, S, SO or S02. In another preferred embodiment, X and Y are taken together with the carbon to which they are attached to form a cyclohexyl, cyclohexenyl, cyclopentyl or cyclopentenyl ring, which are monosubstituted with Z which is selected from the group consisting of OH, R3C (0) 0- , R3C (0) 0- (C? -C6) alkyl-, R2ON = R2ON = (C6C6) alkyl-, R2ON = CR2 (C-C6 alkyl) -; -NR2 (OR2), R4S (0) 2R5N-, and R4S (0) 2R5N-alkyl (d-C6) -; wherein R2, R3, R4 and R5 are as defined above. In another preferred embodiment, X and Y are taken together with the carbon to which they are attached to form a cyclohexyl or cyclopentyl ring, which is monosubstituted with Z which is selected from the group consisting of OH, R3C (0) 0-, R3C (0 ) 0-alkylene (d-Cß) -, R2ON =, R2ON = alkyl (C? -C6) -, R2ON = CR2 (alkyl dC6) -; -NR2 (OR2), R4S (0) 2R5N- and R4S (0) 2R5N-alkyl (d-Cß) -; wherein R2, R3, R4, and R5 are as defined above. In another preferred embodiment, Z is OH. In another preferred embodiment, Z is R3C (0) 0-. In another preferred embodiment, Z is R3C (0) 0-alkyl (d-Ce) -. In another preferred embodiment, Z is R2ON =, R2ON = alkyl (d-Cß) -, or R2ON = CR2 (alkyl d-C6) -. In another preferred embodiment, Z is R2ON =. In another preferred embodiment, Z is -NR2 (OR2). In another preferred embodiment, Z is R4S (0) 2R5N-. In another preferred embodiment, Z is R4S (0) 2R5N (d-C6 alkyl) -. In a non-limiting mode, the process of the present invention can be used to prepare a compound selected from the group by: 4-cyclohexylresorcinol; 4-cyclopentyl resorcinol; 4- (2,4-dihydroxyphenyl) cyclohexanol; 4- (2,4-dihydroxyphenyl) cyclohexanone; oxime of 4- (2,4-dihydroxyphenyl) cyclohexanone; oxime of 0-methyl-4- (2,4-dihydroxyphenyl) cyclohexanone; oxime of 0-benzyl-4- (2,4-dihydroxyphenyl) cyclohexanone; 3- (2,4-dihydroxyphenyl) -2-cyclohexen-1-one; (±) -3- (2,4-dihydroxyphenyl) cyclohexanone; oxime of 3- (2,4-dihydroxyphenyl) -2-cyclohexen-1-one; oxime of (±) -3- (2,4-dihydroxyphenyl) cyclohexanone; (±) -4- [3- (1-piperazinyl) cyclohexyl] -1,3-benzenediol; (±) -N- [3- (2,4-dihydroxyphenyl) cyclohexyl] methanesulfonamide; (±) -4- [3- (hydroxymethyl) cyclohexyl] -1,3-benzenediol; (±) -4- [3- (hydroxyamino) cichlohexyl] -1,3-benzenediol; c / s LtaA7s-4- [4- (hydroxymethyl) cyclohexyl] -1, 3-benzenediol; c / s / iara-4- (4-hydroxy-4-methylcyclohexyl) -1,3-benzenediol; oxime of (±) -0-methyl-3- (2,4-dihydroxyphenyl) cyclohexanone; (±) -3- (2,4-d.hydroxyphenyl) -1-methylenecyclohexanol; oxime of (±) -0-benzyl-3- (2,4-dihydroxyphenyl) cyclohexanone; oxime of 3- (2,4-dihydroxyphenyl) -2-cyclopentanone; (+) - 3- (2,4-dihydroxyphenyl) cyclopentanone; oxime of (±) -3- (2,4-dihydroxyphenyl) cyclopentanone; 4- (2,4-dihydroxyphenyl) -3-cyclohexen-1-one; c / s / fra7s -? / - [4- (2,4-dihydroxyphenyl) cyclohexyl] acetamide; c / 's -? / - [4- (2,4-dihydroxyphenyl) cyclohexyl] -1-butanesulfonamide; Irans -? / - [4- (2,4-dihydroxyphenyl) cyclohexyl] methanesulfonamide; cis-N- [4- (2,4-dihydroxyphenyl) cyclohexyl] methanesulfonamide; 4- [4- (4-hydroxyphenyl) cyclohexyl] -1,3-benzenediol; c / s / lrans- [4- (2,4-dihydroxy-phenyl) -cyclohexyl] -acetate methyl; ioR7S- [4- (2,4-dihydroxyphenyl) cyclohexyl] methyl acetate; c / s- [4- (2,4-dihydroxy-phenyl) -cyclohexyl] -ethyl acetate; i? a / 7s- [4- (2,4-dihydroxyphenyl) cyclohexyl] acetic acid; c / s- [4- (2,4-dihydroxyphenyl) cyclohexyl] acetic acid; c / s / Ira / 7s- [4- (2,4-d.hydroxyphenyl) cyclohexyl] acetic acid; c / * s / frans- [4- (2,4-dihydroxyphenyl) cichlohexyl] acetonitrile; c / s / fra7s- [4- [4- (2-aminoethyl) cyclohexyl] -1, 3-benzenediol; (±) -4- (3,3-difluorocyclohexyl) -1, 3-benzenediol; (±) -3- (2,4-dihydroxy-phenyl) -cyclohexanecarboxamide; (±) -3- (2,4-dihydroxyphenyl) -N-hydroxycyclohexanecarboxamide; (±) -3- (2,4-dihydroxyphenyl) -N-ethylcyclohexanecarboxamide; (±) -4- [3-hydroxy-3- (hydroxymethyl) cyclohexyl] -1,3-benzenediol; (±) -? / - [3- (2,4-dihydroxyphenyl) cyclohexyl] acetamide; 4- (2,4-dihydroxyphenyl) -cyclohexyl-4- (dimethylamino) benzoate; c / 's / i "a7s-4- (2,4-dihydroxyphenyl) cyclohexanecarboxylic acid; 4- (2,4-dihydroxyphenyl) cyclohexyl; frans-cyclohexylcarbamate 4- (2,4-dihydrocarbamate) -dihydroxyphenyl) cyclohexyl]; 4- (2,4-dihydroxyphenyl) -cyclohexyl-trans-4-tert-butyl-benzoate; 4- (2,4-dihydroxyphenyl) -cyclohexyl-trans-4-fluoro-benzoate; 4- trans-4-trifluoromethyl-benzoate; (2,4-Dihydroxy-phenol) cyclohexyl; trans-4-methoxy-benzoate of 4- (2,4-dihydroxyphenyl) -cyclohexyl; 4- (2,4-dihydroxyphenyl) -cyclohexyl-4-methyl-benzoate; -chlorobenzoate of 4- (2,4-dihydroxyphenyl) cyclohexyl; 4- (2,4-dihydroxyphenyl) cyclohexyl frans-3,4-dimethylbenzoate; fra / 7s-3,4-dichlorobenzoate of 4- (2,4-dihydroxyphenyl) cyclohexyl; frans-4- [4- (phenylsulfonyl) cyclohexyl] -1,3-benzenediol; Ira7s-4- [4- (phenylsulfonyl) cyclohexyl] -1,3-benzenediol; 4- [2,4-dihydroxyphenyl) cyclohexyl] methyl propionate; Ethyl 4- (2,4-dihydroxyphenyl) -1-hydroxycyclohexanecarboxylate; c / s frans-4- [4- (hydroxyamino) -cyclohexyl] -1,3-benzenediol; frans-4- [4- (methoxyamino) cyclohexyl] -1,3-benzenediol; and their pharmaceutically acceptable salts. The term "resorcinol derivative", as used herein, refers to a compound comprising a monosubstituted resorcinol ring in the 4-position, as defined above, and is represented by the structure of formula I. The expression "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, branched, cyclic moieties or combinations thereof, which may or may not be more substituted. Any substituent or functional group on the alkyl group, as indicated herein, may be substituting the alkyl group at any place where substitution is possible. The term "aryl", as used herein, refers to phenyl or naphthyl optionally substituted with one or more substituents, preferably from zero to two substituents, independently selected from halogen, OH, alkyl (d-C6), alkoxy (C? -C6), amino, alkylamino (C? -C6), di- (alkylamino (CrC6), nitro, cyano or trifluoromethyl Any substituent or functional group on the aryl group, as indicated herein, may be substituting anywhere in the aryl group The term "one or more substituents", as used herein, refers to a number of substituents that includes from one the maximum number of substituents possible based on the number of binding sites The term "halogen", as used herein, refers to halogen, and unless otherwise indicated, includes chlorine, fluorine, bromine and iodine. The term "acyl", as used herein , unless where otherwise indicated, it includes a radical of the general formula RCO, in which R is alkoxy alkyl, aryl, arylalkyl or arylalkyloxy, and the expressions "alkyl" or "aryl" are as defined above. The term "acyloxy," as used herein, includes O-acyl groups, in which "acyl" is as defined above. The term "(C2-Cg) heterocycloalkyl", when used herein, refers to pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziridinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidinyl, 1,3-oxazolidin-3. -yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, , 3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, piperazinyl, chromanyl, etc. Those skilled in the art will understand that the connection of said heterocycloalkyl (C2-C9) ring can be accomplished through a carbon atom or through a nitrogen heteroatom, when possible. The term "heteroaryl (C2-Cg)", when used herein, refers to furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1, 3,5-oxadiazolyl. 1, 2,4-oxadiazolyl, 1,3-oxadiazolyl, 1, 3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,4-triadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, 1 , 2,4-triazinyl, 1, 2,3-triazinyl, 1, 3,5-triazinyl, pyrazolo [3,4-bjpyridinyl, cinolinyl, pteridinyl, purinyl, 6,7-dihydro-5H- [1] pyridinyl, benzo [b] thiophenyl, 5,6,7,8-tetrahydroquinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, tianaphtenyl, isothianaphtenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolyl, indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, benzoxazinyl, etc. Those skilled in the art will understand that the connection of said heterocycloalkyl (C2-Cg) rings can be accomplished through a carbon atom or through a nitrogen heteroatom, when possible. The compounds of formula I may contain chiral centers and, therefore, may exist in different enantiomeric and diastereomeric forms. This invention relates to the preparation of all optical isomers, stereoisomers and tautomers of the compounds of formula I and mixtures thereof. Formula I, as defined above, also includes compounds identical to those depicted, except for the fact that one or more hydrogen atoms, carbon or other atoms are substituted by their isotopes. These compounds can be useful as research and diagnostic tools, in pharmacokinetic studies of metabolism and in binding assays. The present invention also relates to the preparation of pharmaceutically acceptable acid addition salts and base addition salts of any of the compounds of formula I mentioned above. The acids which are used to prepare the pharmaceutically acceptable addition salts of the above-mentioned basic compounds of this invention are those which form non-toxic acid addition salts, ie salts containing pharmaceutically acceptable anions, such as the hydrochloride salts , hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e., 1,1-methylene-bis- (2-hydroxy-3-naphthoate)).

The present invention also provides various intermediate compounds, useful in the preparation of a wide variety of resorcinol derivatives.

The present invention provides an intermediate compound of formula (4), wherein W, X and Y are as defined above. (4) In a preferred embodiment, the intermediate compound of formula (4) has the structure of formula (4a), wherein W is as defined above, and n is 0, 1, 2 or 3. In another preferred embodiment, the intermediate of formula (4) has the structure of formula (4b) or (4c), in which W is as defined above. In another preferred embodiment, the intermediate compound of formula (4) has the structure of formula (4d), wherein W and Z are as defined above, and n is 0, 1, 2 or 3. In another preferred embodiment, the intermediate of formula (4) has the structure of formula (4e) or (4f), in which W and Z are as defined above. In another preferred embodiment, the intermediate compound of formula (4) has the structure of formula (4g), in which W and each Z are as defined above, and n is 0, 1, 2 or 3.

In another preferred embodiment, the intermediate compound of formula (4) has the structure of formula (4h) or (4i), in which W and each Z are as defined above. The present invention further provides an intermediate compound of formula (5), (5) in which Q, W, X and Y are as defined above. In a preferred embodiment, the intermediate compound of formula (5) has the structure of the formula (5a), wherein Q and W are as defined above, and n is 0, 1, 2 or 3. In another preferred embodiment, the intermediate of formula (5) has the structure of formula (5b) or (5c), in which Q and W are as defined above. In another preferred embodiment, the intermediate compound of formula (5) has the structure of formula (5d), wherein Q, W and Z are as defined above, and n is 0, 1, 2, or 3. In another preferred embodiment, the intermediate of formula (5) has the structure of formula (5e) or (5f) ), in which Q, W and Z are as defined above.

In another preferred embodiment, the intermediate compound of formula (5) has the structure of formula (5g), wherein Q, W and Z are as defined above, and n is 0, 1, 2 or 3. In another preferred embodiment, the intermediate compound of formula (5) has the structure of formula (5h) or (5i) , in which Q, W and each Z are as defined above. The present invention further provides an intermediate compound of formula (5 '), in which Q, X and Y are as defined above.

In another preferred embodiment, the intermediate compound of formula (5 ') has the structure of formula (5'a), wherein Q is as defined above, and n is 0, 1, 2 or 3. In another preferred embodiment, the intermediate of formula (5 ') has the structure of formula (5'b) or (5'c) ), in which Q is as defined above. In another preferred embodiment, the intermediate compound of formula (5 ') has the structure of formula (5'd) or (5'e), in which Q and Z are as defined above. In another preferred embodiment, the intermediate compound of formula (5 ') has the structure of formula (5'f) or (5'g), in which Q and each Z are as defined above.

DETAILED DESCRIPTION OF THE INVENTION The process of the present invention is described in the following reaction and analysis schemes.

SCHEME 1 SCHEME 2 l (c) (12) (11) Referring to scheme 1, the compounds of formula (2) can be prepared starting with the compound (1), which is commercially available (Aldrich Chemical Co.). A suitable protecting group can be selected, as will be apparent to those skilled in the art. An example of a suitable protecting group is benzyl. The conversion to the compounds of formula (2) can be carried out under conventional conditions. For example, when the protecting group is benzyl, condensation may occur between the compound (1) and the benzyl alcohol with the removal of the water using a Dean-Stark apparatus. The condensation of the compounds of formula (2) with the compounds of formula (3) can be produced using conventional techniques, for example, the treatment of the compounds of formula (2) with a base, such as lithium diisopropylamide or lithium hexamethyldisilazide, in an ethereal solvent followed by the addition of a compound of formula (3), produces the compounds of formula (4). When W is H, the condensation of the compounds of formula (2) with the compounds of formula (3) requires the use of at least two equivalents of a suitable base, such as lithium diisopropylamide, in a suitable solvent such as tetrahydrofuran, with a suitable cosolvent such as hexamethylphosphoramide. Treatment of the compounds of formula (4) with a suitable halogenating reagent such as for example? / -bromosuccinimide in a chlorinated solvent, such as dichloromethane or chloroform, at about room temperature, can produce the compounds of formula (5) wherein Q is halo, and preferably bromine. When W is H, the compound of formula (5) may exist in equilibrium with the compound of formula (5 '). Alternatively, when W is H, the compounds of formula (5 ') can be prepared directly from the compounds of formula (4) by treating the compound of formula (4) with a suitable halogenating agent. It is intended that the process of the present invention include each of these various synthetic routes. The compounds of formula (6) can then be generated from the compounds of formula (5) or (5 ') under suitable conditions. These conditions may involve treating the compounds of formula (5) or (5 ') with a base, such as 1, 8-diazobicyclo [5.4.0] undec-7-ene, in a suitable solvent as? /, / V -dimethylformamide at about room temperature. The compounds of formula I (a) can be generated using conventional techniques, for example treating the compounds of formula (6) with triethylsilane in the presence of a Lewis acid such as boron trifluoride, in a chlorinated solvent, followed by suitable conditions to eliminate the protecting group, or hydrogenating the compounds of formula (6) under conventional conditions, which generates the compounds of formula I (a). The compounds of formula (7) can be generated from the compounds of formula (5), (5 ') or (6) under suitable reaction conditions. These conditions may involve treating the compounds of formula (5), (5 ') or (6) with a base such as 1, 8-diazobicyclo [5.4.0] undec-7-ene, in a suitable solvent as V, ? / - dimethylformamide at about 140 ° C. Other solvents such as toluene or N-methylpyrrolidinone may also be useful for this purpose. By subjecting the compounds of formula (7) to conventional hydrogenation conditions, for example gaseous hydrogen and palladium on carbon in ethanol, the compounds of general formula I (a) are produced, in which the protecting group is benzyl. When W is a protecting group, the compounds of formula I (b) can be formed by treating the compounds of formula (7) under conventional conditions, which will be apparent to those skilled in the art. The compounds of formula I (b) can in turn be converted to the compounds of formula I (a) by conventional hydrogenation conditions, as described above. The compounds l (a) and l (b) are within the scope of formula I. Referring to scheme 2 as an example of a more specific scheme, the compounds of formula (8) can be prepared starting with compound (1), which is available in the market (Aldrich Chemical Co.). The conversion to the compounds of formula (8) can be carried out under conventional conditions, for example, when the protecting group is benzyl, condensation can occur between the compound (1) and the benzyl alcohol with the elimination of the water using a Dean-Stark apparatus. The condensation of the compounds of formula (8) with the compounds of formula (9) can be produced using conventional techniques, for example, the treatment of the compounds of formula (8) with a base, such as lithium diisopropylamide, in an ethereal solvent followed by the addition of a compound of formula (9), produces the compounds of formula (10). The treatment of the compounds of formula (10) with a suitable brominating reagent such as for example / V-bromosuccinimide in a chlorinated solvent at about room temperature, can produce the compounds of formula (11). The compounds of formula (12) can then be generated from the compounds of formula (11) under suitable reaction conditions. These conditions may involve treating the compounds of formula (11) with a base, such as 1, 8-diazobicyclo [5.4.0] undec-7-ene, in a suitable solvent such as N, N-dimethylformamide at about 140 ° C. . By subjecting the compounds of formula (12) to conventional hydrogenation conditions, for example gaseous hydrogen and palladium on carbon in a mixture of ethanol / tetrahydrofuran, the compounds of general formula I (c) are produced, in which the protective group is benzyl The compounds of formula I (d) can then be obtained by subjecting the compounds of formula I (c) to acidic conditions. The compounds l (c) and l (d) are both within the scope of formula I. Those skilled in the art will know that in the processes described above, the functional groups of the intermediates may require protection. The use of protecting groups is well known in the art, and is described in depth, among others, in: Protecting Groups in Organic Chemistry. J.W.F. McOmie (ed.), 1973, Plenum Press; and Protecting Groups in Organic Synthesis. 2nd edition, T.W. Greene and P.G.M. Wutz, 1991, Wiley-lnterscience, which are incorporated herein by reference in their entirety. The resorcinol derivatives prepared according to the process described herein are useful for all the purposes previously described for this type of compounds. For example, resorcinol derivatives useful as skin lightening agents or for other cosmetic purposes can be prepared according to the process of the present invention. When the resorcinol derivatives prepared according to the present invention are useful as skin lightening agents, they can be used to treat human pigmentation disorders, including simple and solar freckles (including age / liver spots), melasma / chlorasma and post-inflammatory hyperpigmentation. These compounds reduce melanin levels in the skin by inhibiting the production of melanin, whether it occurs constitutively or as a response to UV irradiation (such as sun exposure), and typically by the inhibition of the tyrosinase enzyme. The active skin lightening compounds prepared according to the present invention can be used to reduce the melanin content of the skin in non-pathological states, to induce a lighter skin tone, as desired by the user, or to prevent the accumulation of melanin in the skin that has been exposed to UV irradiation. They can also be used in conjunction with skin peeling agents (including glycolic acid or trichloroacetic acid face scrubs) to lighten skin tone and prevent repigmentation. The appropriate dosage regimen, the amount of each dose administered and the specific intervals between the doses of the active ingredient will depend on the particular active ingredient used, the disorder of the patient being treated, and the nature and severity of the condition or disorder that is being treated. It is being treated. Preferably, the active ingredient is administered in an amount and with a range that results in the desired treatment or improvement in the condition or disorder being treated. An active principle prepared according to the process of the present invention can also be used together with sunscreens (UVA or UVB blockers) to prevent repigmentation, to protect from the sun or UV-induced skin darkening, or to improve its ability to reduce the melanin of the skin and its bleaching action of the skin. An active ingredient prepared according to the process of the present invention can also be used together with the retinoic acid or its derivatives, or any compound that interacts with the retinoic acid receptors, and accelerates or improves the ability of the invention to reduce melanin in the skin and the bleaching action of the skin, or improves the ability of the invention to prevent the accumulation of melanin in the skin. An active principle prepared according to the present invention can also be used together with 4-hydroxyanisole. An active ingredient prepared according to the process of the present invention can also be used together with ascorbic acid, its derivatives and products based on ascorbic acid (such as magnesium ascorbate) or other products as an antioxidant mechanism (such as resveratrol) that accelerate or They improve their ability to reduce melanin in the skin and its blocking action on the skin. The active ingredients for skin lightening prepared according to the present invention are generally administered in the form of pharmaceutical compositions comprising at least one of the compounds of formula (I), together with a pharmaceutically acceptable carrier or diluent. These compositions are generally formulated in a conventional manner using solid or liquid carriers or diluents as appropriate for topical administration, in the form of solutions, gels, creams, jellies, pastes, lotions, ointments, ointments, sprays and the like. Examples of vehicles for the application of the active principles of this invention include an aqueous or water-alcohol solution, an oil-in-water or water-in-oil type emulsion, an emulsified gel or a two-phase system. Preferably, the compositions according to the invention are in the form of lotions, creams, milks, gels, masks, microspheres or nanospheres, or vesicular dispersions. In the case of vesicular dispersions, the lipids forming the vesicles may be of ionic or non-ionic type, or a mixture of both. In a skin lightening composition comprising a resorcinol derivative prepared according to the process of the present invention, the concentration of the resorcinol derivative in general is between 0.01 and 10%, preferably between 0.1 and 10%, based on the total weight of the resorcinol derivative. the composition. A resorcinol derivative for lightening the skin prepared according to the present invention can be conveniently identified by its ability to inhibit the tyrosinase enzyme, as determined by any conventional assay, such as those described below. 1. Tyrosine assay (DOPA-oxidase) using a cell lysate The human melanoma cell line SKMEL 188 (licensed by Memorial Sloan-Kettering) is used in the cell lysate assay and selection. In the assay, the compounds and L-dihydroxyphenylalanine (L-DOPA) (100 μg / ml) are incubated with cell lysates containing human tyrosine, for 8 hours before the plates are read at 405 nm. The pharmacological potency of the compounds in the DOPA-oxidase assay correlates very well with that of the tyrosine-hydroxylase assay using 3H-tyrosine as the substrate. 2. Melanin assay in human primary melanocytes The compounds are incubated as primary human melanocytes in the presence of an α-melanocyte stimulating hormone (a-MSH) for 2-3 days. The cells are then lysed with sodium hydroxide and sodium dodecylsulfate (SDS), and the melanin signals are read at 405 nm. Alternatively, 14C-DOPA is added to the cells along with tyrosinase inhibitors, and the insoluble 14C-melanin in acids is quantified by a scintillation counter. The IC50 reflect the inhibitory potency of the compounds in the new melanin synthesis that has been stimulated by a-MSH. 3. Tyrosine kinase assay (TK) TK assays can be carried out using the purified tyrosine kinase domains c-met, erb-B2 or IGF-r. In the assay, a specific antibody against the phosphorylated tyrosine residue is used. The colorimetric signals are generated by horseradish peroxidase, which is conjugated with the antibody. 4. Equivalent model of human skin A mixture of keratinocytes and human melanocytes is grown in an air-liquid interface. This tissue culture forms a three-dimensional structure that histologically and microscopically resembles the epidermis of human skin. The test compounds are added on top of the cells to mimic the topical application of the drug. After incubation with the compounds (10 μM) for 3 days, the cells are washed thoroughly and lysed for the DOPA-oxidase assay.

. IL-1 assay (interleukin-1 assay) An IL-1a ELISA assay (R & D system) can be used to evaluate the effect of the compounds on the secretion of I L-1 in a model equivalent to human skin. . IL-1a is a proinflammatory cytokine and plays a role in UV-induced skin inflammation. 6. In vivo studies In this study, black or dark brown guinea pigs with a homogenous skin color can be used. A solution of the test compound of formula I (5% in propylene glycol ethanol 70:30) and the control vehicle are applied to the animals twice daily, 5 days a week for 4-8 weeks. Using this assay, depigmentation can be determined by subtracting the light reflectance from the untreated skin, from the reflectance of the light from the treated skin. The present invention is illustrated by the following examples. However, it should be understood that the invention is not limited to the specific details of these examples. The melting points are uncorrected. The proton nuclear resonance spectra (1 H NMR, 400 MHz) were measured for solutions in d6-DMSO, CDCI3 or d4-MEOH, and the peak positions are expressed in parts per million (ppm) downfield of tetramethylsilane ( TMS). The shapes of the peaks were indicated as follows: s, singlet; d, doublet; t, triplet; q, quadruple; m, multiplet; a, wide. The following examples are illustrative only, and are not intended to limit the scope of the present invention.

EXAMPLE INTERMEDIATE 1 3- (benzyloxy) -2-cyclohexen-1-one To a round bottom flask equipped with a magnetic stirrer and a Dean-Stark apparatus was added 1,3-cyclohexanedione (70.0 g, 624 mmol), toluene (500 ml), p-toluenesulfonic acid monohydrate (1.68 g, 8.83 mmol). ) and benzyl alcohol (65.6 g, 606 mmol). The resulting solution was heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and washed with a saturated sodium carbonate solution (4 x 50 ml). The organic layer was washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated in vacuo, yielding a brown oil which crystallized on standing. The crude crystalline material was suspended in isopropyl ether (100 ml) and stirred at 0 ° C for 2 hours. The mixture was filtered and the crystalline material was washed with ice-cooled isopropyl ether (3 x 100 ml), followed by cold petroleum ether (100 ml). The resulting solid was dried overnight under reduced pressure to yield the title compound (85.3 g, 68%). m / z (ES +) 203 (M + H +).

INTERMEDIATE 2 (±) -3- (benzyloxy) -6- (8-hydroxy-1,4-dioxaspirof4.51dec-8-yl) -2-cyclohexen-1-one To a round bottom flask equipped with a magnetic stirrer was added anhydrous tetrahydrofuran (600 ml) and diisopropylamine (38.1 ml, 272 mmol). The stirred solution was cooled to -78 ° C, and n-butyllithium (113.4 ml, 272 mmol, 2.4 M in hexanes) was added dropwise via syringe in 20 ml portions. The resulting yellow solution was stirred for 35 minutes at -78 ° C, and then 3- (benzyloxy) -2-cyclohexen-1-one (50.0 g, 248 mmol) was added as a solution in anhydrous tetrahydrofuran (100 ml). The solution was stirred for 1 hour before the addition of cyclohexane-1,4-dione monoethylene ketal (38.7 g, 248 mmol) as a solution in anhydrous tetrahydrofuran (100 ml). The solution was stirred for 2 hours at -78 ° C, then allowed to warm slowly to room temperature for 1 hour. Saturated aqueous ammonium chloride (80 ml) was added, followed by dichloromethane (700 ml) and the mixture was stirred until no solids remained. The layers were separated and the aqueous phase was extracted with dichloromethane (2 x 100 ml). The combined organic layers were washed with brine (50 ml), dried over magnesium sulfate, and then concentrated in vacuo. Trituration of the resulting solid with methanol afforded the title compound (78.4 g, 88%). m / z (ES +) 359 (M + H +).

INTERMEDIATE 3 (+) - 1 - (benzyloxy) -6-bromo-3- (1,4-dioxaspiro [4.5] dec-8-yl) -2- oxabicyclo [2.2.2] octan-5-one A round bottom flask equipped with a magnetic stirrer was charged with (+) - 3- (benzyloxy) -6- (8-hydroxy-1,4-dioxaspiro [4.5] dec-8-yl) -2-cyclohexen-1 -one (78.4 g, 219 mmol) and dichloromethane (600 ml). To the stirred solution was added N-bromosuccinimide (40.9 g, 230 mmol) in one portion, followed by hydrobromic acid (3 drops, 48% aqueous solution). The resulting solution was stirred at room temperature for 2 hours, then poured into a separatory funnel containing a solution of aqueous sodium metabisulfite (150 ml) and dichloromethane (200 ml), and the funnel was vigorously stirred. The layers were separated and the organic layer was washed with brine (200 ml), dried over magnesium sulfate, filtered and then concentrated in vacuo to yield a solid. Trituration with methanol (500 ml) afforded the title compound (82.8 g, 86%) as a white solid. m / z (ES +) 437 and 439 [(1: 1), M + H +].

INTERMEDIATE 4 5- (benzyloxy) -2- (1,4-dioxaspiro [4.5] dec-7-en-8-yl) -phenol A round bottom flask was charged with (±) -1- (benzyloxy) -6-bromo-3- (1,4-dioxaspiro [4.5] dec-8-yl) -2-oxabicyclo [2.2.2] octane- 5-one (36 g, 82.4 mmol) and / V, / V-dimethylformamide anhydrous (300 ml). To the stirred solution was added 1,8-diazabicyclo [5.4.0] undec-7-ene (13.6 ml, 90.6 mmol) in one portion, before heating to 140 ° C for 19 hours with vigorous stirring. The reaction mixture was allowed to cool to room temperature, and most of the solvent was removed under reduced pressure. The remaining oil was partitioned between dichloromethane (500 ml) and water (100 ml), and the layers were separated. The organic phase was washed with water (2 x 100 ml) followed by brine (100 ml). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to give a brown solid which was adsorbed on silica gel. Purification by resolution chromatography (SIO2, dichloromethane then ethyl acetate / petroleum ether, 3: 7, v / v) yielded an off-white solid which was suspended in methanol (150 ml). The suspension was stirred for 20 minutes, filtered and washed with methanol (50 ml). The title compound (18.2 g, 65%) was isolated as a white solid after removal of excess solvent under reduced pressure, m / z (ES +) 339 (M + H +).

EXAMPLE 1 4- (1,4-dioxaspiro [4.5] dec-8-yl) -1,3-benzenediol A round bottom flask equipped with a magnetic stirrer was charged with 5- (benzyloxy) -2- (1,4-dioxaspiro [4.5] dec-7-en-8-yl) phenol (14.5 g, 42.8 mmol) and tetrahydrofuran (50 mL). The stirred mixture was heated gently until a solution formed, after which the solution was allowed to cool to room temperature. Ethanol (100 ml) and palladium (4.54 g, 10% on activated carbon) were added sequentially. The reaction vessel was then placed under vacuum, placed under a hydrogen atmosphere and stirred vigorously for 24 hours. The reaction mixture was filtered through a pad of celite, washing with ethyl acetate. The filtrate was concentrated in vacuo to yield an off-white solid. The crude sodium was suspended in dichloromethane (200 ml), then collected on a sinter, yielding the title compound (10.2 g, 95%) as a white solid. m / z (ES +) 251 (M + H +).

EXAMPLE 2 4- (2,4-dihydroxyphenyl) cyclohexanone A round bottom flask equipped with a magnetic stirrer was charged with 4- (1,4-dioxaspiro [4.5] dec-8-yl) -1,3-benzenediol (11.3 g, 45.2 mmol), acetone (250 ml) and water (50 ml). To the stirred solution was added pyridinium p-toluenesulfonate (1.14 g, 4.52 mmol) in one portion and then the reaction mixture was heated to reflux for 8 hours. After allowing the reaction mixture to cool to room temperature, most of the acetone was removed in vacuo and the remainder of the mixture was partitioned between ethyl acetate (200 ml) and water (50 ml). The aqueous layer was extracted with ethyl acetate (3x50 ml) and the combined organic layers were washed with brine (30 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield an off-white powder. After washing the powder with dichloromethane (100 ml) and removing the excess solvent under reduced pressure, the title compound (9.30 g, 100%) was obtained as an off-white powder. m / z (ES +) 207 (M + H +); dH (CD3OD) 1.84-1.97 (2H, m), 2.15-2.23 (2H, m), 2.36-2.45 (2H, m), 2.58-268 (2H, m), 3.39 (1H, tt), 6.26 ( 1 H, dd), 6.34 (1 H, d), 6.96 (1 H, d). All patents, patent applications and publications cited above are incorporated herein by reference in their entirety.

The scope of the present invention should not be limited by the specific embodiments described herein, which are intended to be unique illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those indicated and described herein, will become apparent from the description above to those skilled in the art. It is intended that these modifications be within the scope of the appended claims.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A process for preparing a compound of formula (6) (6) wherein W is hydrogen or a protecting group; wherein X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C2) alkynyl, or X and Y are taken together with the carbon to which they are attached; joined to form a cycloalkyl ring (d-Cs) or a cycloalkenyl ring (Cs-Cs) with the proviso that the cycloalkyl ring (d-Cs) or the cycloalkenyl ring (C5-Cs) are not aromatic; and wherein the alkyl (CrC2), alkenyl (C2-C2), alkynyl (C2-C2), the cycloalkyl ring (d-Cs) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyl (CrCe); aryl, heterocycloalkyl (d-Cg); heteroaryl (d-Cg); aryl (alkyl d-Ce) -; = 0; = CHO (alkyl d-d); amino: hydroxy; alkoxy (Cr d); aryl (alkoxy (dd) -; acyl (dd); alkylamino (dd) -; aryl (C C6 alkylamino) - aminoalkyl (d-C6) -: (d-C6) alkoxy -CO-NH-; alkylamino (d) -C6) -CO-; alkenyl (dd alkynyl (d-dKydroxyalkyl (C Ce) -; (alkoxy dd) (C Ce alkyl) -; (acyloxy dd) (dd alkyl) -; nitro; cyanoalkyl (dd) -; haloalkyl (CrCe) -; nitroalkyl (CrCe) - trifluoromethyl; trifluoromethyl (alkyl dd) -; acylamino (CrCe) -; (acylamino dd) (alkyl dd) -; (alkoxy dd) (acylamino CrCe) -; aminoacyl (dd) -; (aminoacyl dd) (alkyl (dd) -; (alkylamino dd) (acyl d-Ce) -; (Cr) 2 aminoacyl (d-Ce) -; -CO2R2; -alkyl (d-C6) -C02R2; -C ( 0) N (R2) 2: -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = (C6) alkyl-; R2ON = CR2 (alkyl dd) -; NR2 (OR2); -alkyl (d-d) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (d-C6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is selected independently between hydrogen, alkyl (dd), aryl or aryl (alkyl dd) -; R3C (0) 0-, and R3 is alkyl (dd), aryl or aryl (alkyl dd) -; R3C (0) 0 -alkyl (d-C6) -; R4R5N-C (0) -0-; R -R5NS (0) 2- R4R5NS (0) 2- (alkyl d-C6) -; R4S (0) 2R5N-; R4S (O ) 2R5N (C6 alkyl) -; and m is 0, 1 or 2, and R4 and R5 are each selected independent between hydrogen or alule (d-d) -; -C (= NR6) (N (R4) 2); -alkyl (d-C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (O) aryl (alkyl d-d); -NH (C6 alkyl); aryl (alkyl d-d) - HN-; and a ketal; which comprises reacting a compound of formula (5) or (5 ') (5) (5 ') in which Q is halogen, and W, X and Y are as defined above, with a base to form the compound of formula (6).

2. The process according to claim 1, wherein Q is bromine, iodine or chlorine.

3. The process according to claim 1, wherein Q is bromine.

4. A process for preparing a compound of formula (7) (7) wherein W is hydrogen or a protecting group; in which X and Y are they each independently select from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-d2) alkynyl, or X and Y are taken together with the carbon to which they are attached to form a cycloalkyl ring (dd) or a cycloalkenyl ring (Cs-Ce), with the proviso that the cycloalkyl ring (dd) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and wherein the alkyl (dC? 2), alkenyl (C2-C? 2), alkynyl (C2-C? 2), the cycloalkyl ring (d-Cs) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyl (CrCe); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-Cg); aryl (alkyl (Crd) -; = 0; = CHO (alkyl (d-d) -; amino; hydroxy; alkoxy (d-d); aryl (d-alkoxy) -; acyl (CrCe); alkylamino (CrCe) -; aryl (alkylamino d-d) -; aminoalkyl (d-d) -; alkoxy (Crd) -CO-NH-; alkylamino (C? -d) -CO-; alkenyl (d-d); alkynyl (C2-d) -; hydroxyalkyl d-C6) -; (C6 alkoxy) (d-Ce alkyl) -; (acyloxy d-d) (alkyl d-d) -; nitro; cyanoalkyl (d-d) -; haloalkyl (CrCe) -; nitroalkyl (d-d) -; trifluoromethyl; trifluoromethyl (CrCe alkyl) -; acylamino (d-d) -; (acylamino d-d) (alkyl d-Ce) -; (alkoxy d-d) (acylamino d-d) -; aminoacyl (CrC6) -; (aminoacyl d-d) (alkyl d-d) -; (alkylamino d-d) (acyl CrCe) -; (alkyl d-C6) 2-aminoacyl (CrC6) -; -CO2R2; -alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (d-C6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (Ci-Ce) -; R2ON = CR2 (alkyl (d-C6) -; -NR2 (0R2); -alkyl (Crd) -NR2 (0R2); -C (O) (NR20R2); -alkyl (-d) -C (O) ( NR20R2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl, alkyl (dd), aryl or aryl (alkyl dd) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R3C (O) 0-alkyl (CrC6) -; R4R5N-C (0) -O-; R4-R5NS (0) 2- R4R5NS (0) 2 (alkyl d- C6) -; R4S (0) 2R5N-; RS (0) 2R5N (alkyl dd) -; and m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (dd); -C ( = NR6) (N (R4) 2); -alkyl (d-C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC ( O) aryl (CrCe alkyl); -NH (alkyl dd); aryl (alkyl dd) -HN-; and a ketal, which comprises reacting a compound of formula (5) or (5 ') in which Q is halogen, and W, X and Y are as defined above, with a base to form the compound of formula (7).

5. The process according to claim 4, wherein Q is bromine, iodine or chlorine.

6. The process according to claim 4, wherein Q is bromine.

7 '.- The process according to claim 1 or claim 4, in wherein the compound of formula (5) is prepared by reacting the compound of formula (4) (4) in which W, X and Y are as defined above, with a halogenating agent to form the compound of formula (5).

8. The process according to claim 7, wherein the halogenating agent is a brominating agent.

9. The process according to claim 8, wherein the brominating agent is N-bromosuccinimide.

10. The process according to claim 7, wherein the compound of formula (4) is prepared by reacting a compound of formula (2) (2) with a compound of formula (3) (3) in which W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).

11. A process for preparing a compound of formula (5) (5) in which Q is halogen; wherein W is a protecting group; wherein X and Y are each independently selected from hydrogen, alkyl (d-C12), alkenyl (C2-C12), alkynyl (C2-C? 2), or X and Y are taken together with the carbon to which they are bound to form a cycloalkyl ring (dd) or a cycloalkenyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (d-d) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and wherein (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, the cycloalkyl ring (C4-Cs) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three Z groups independently selected, and Z is selected from the group consisting of cyano; halo; alkyl (d-d); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-d); aryl (alkyl d-d) -; = 0; = CHO (CrCe alkyl); Not me; hydroxy; alkoxy (CrCe); aryl (CrCe alkoxy) -; acyl (d-d); alkylamino (d-d) -; aryl (alkylamino d-d) -; aminoalkyl (d-d) -; alkoxy (CrCe) -CO-NH-; alkylamino (CrC6) -CO-; alkenyl (C2-C6); (C2-C6) alkynyl; hydroxyalkyl (d-C6) -; (alkoxy d-d) (alkyl d-d) -; (acyloxy d-d) (d-C6 alkyl) -; nitro; cyanoalkyl (d-d) -; haloalkyl (d-Ce) -; nitroalkyl (d-d) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (d-d) -; (acylamino d-d) (alkyl d-Ce) -; (alkoxy d-d) (acylamino CrCe) -; aminoacyl (d-d) -; (aminoacyl CrCe) (alkyl d-d) -; (alkylamino d-d) (acyl d-d) -; (C 1 -C 6 alkyl) 2 aminoacyl (d-Ce) -; -C02R2; -alkyl (d-C6) -C02R2; -C (0) N (R2) 2; -alkyl (d-d) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (Ci-Ce) -; R2ON = CR2 (alkyl dC6) -; -NR2 (0R2); -alkyl (C? -C6) -NR2 (0R2); -C (O) (NR20R2); -alkyl (C C6-C (0) (NR20R2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (dd), aryl or aryl (alkyl dd) -; R3C (0) 0- and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R3C (0) 0 -alkyl (C C6) -; R4R5N-C (0) -0-; R4-R5NS (0) 2 - R4R5NS (0) 2 (Ci-Ce alkyl) -; R4S (0) 2R5N-; R4S (0) 2R5N (d-C6 alkyl) -; and m is 0, 1 or 2, and R4 and R5 are each selected independently from hydrogen or alkyl (dd); -C (= NR6) (N (R4) 2); -alkyl (CrC6) -C (= NR6) (N (R4) 2), and Rd represents OR2 or R2, and R2 is as defined above: -OC (0) aryl (alkyl dd); -NH (alkyl dd); aryl (alkyl dd) -HN-; and a ketal, which comprises reacting a compound of formula (4) (4) wherein W, X and Y are as defined above, with a halogenating agent to form the compound of formula (5).

12. The process according to claim 11, wherein the halogenating agent is a brominating agent.

13. The process according to claim 12, wherein the brominating agent is N-bromosuccinimide.

14. The process according to claim 11, wherein the compound of formula (4) is prepared by reacting a compound of formula (2) (2) with a compound of formula (3) (3) in which W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).

15. - A process for preparing a compound of formula (5 ') wherein Q is halogen; wherein X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, or X and Y are taken together with the carbon to which they are attached to form a cycloalkyl ring (dd) or a cycloalkenyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (d-d) or the cycloalkenyl ring (d-d) are not aromatic; and wherein (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, the cycloalkyl ring (dd) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three Z groups independently selected, and Z is selected from the group consisting of cyano; halo; alkyl (d-d); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-Cg); aryl (alkyl d-d) -; = 0; = CH0 (alkyl d-d); Not me; hydroxy; alkoxy (d-d); aryl (d-alkoxy) -; acyl (d-d); alkylamino (d-d) -; aryl (alkylamino d-C6) -; aminoalkyl (CrCe) -; alkoxy (d-Ce) -CO-NH-; alkylamino (Crd) -CO-; alkenyl (C2-d); alkynyl (d-d); hydroxyalkyl (CrCe) -; (alkoxy d-d) (alkyl d-d) -; (acyloxy Crd) (alkyl CrCe) -; nitro; cyanoalkyl (CrCe); haloalkyl (CrCe) -; nitroalkyl (Crd) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (CrCe) -; (Acylamino CrdXalkyl C Ce) -; (alkoxy d-d) (acylamino d-d) -; aminoacyl (CrCe) -; (aminoacyl Crd) (alkylCe) -; (alkylamino d-dXacyl d-Ce) -; (CrC6 alkyl) 2aminoacyl (CrCe) -; CO2R2; alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (Ci-Ce alkyl) -; NR2 (0R2); -alkyl (C C6) -NR2 (0R2); -C (O) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (Crd), aryl or aryl (CrC6 alkyl) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R 3 C (0) 0-alkyl (d-C 6) -; R4R5N-C (0) -0-; R 4 -R 5 NS (0) 2-R R 5 NS (0) 2 (alkyl d-C 6) -; R4S (0) 2R5N-; R4S (0) 2N (Ci-Ce alkyl) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (d-d); -C (= NR6) (N (R4) 2); -alkyl (CrC6) -C (= NR6) (N (R) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (alkyl d-d); -NH (CrCe alkyl); aryl (alkyl d-d) -HN-; and a ketal; which comprises reacting a compound of formula (4) (4) in which W is H, and X and Y are as defined above, with a halogenating agent to form the compound of formula (5 ').

16. The process according to claim 15, wherein the halogenating agent is a brominating agent.

17. The process according to claim 16, wherein the brominating agent is N-bromosuccinimide.

18. - The process according to claim 15, wherein the compound of formula (4) is prepared by reacting a compound of formula (2) (2) with a compound of formula (3) (3) wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).

19. A process for preparing a compound of formula (4) (4) wherein W is hydrogen or a protecting group; wherein X and Y are each independently selected from hydrogen, alkyl (CrC? 2), alkenyl (C2-d2), alkynyl (C2-C? 2), or X and Y are taken together with the carbon to which they are joined to form a cycloalkyl ring (d-C8) or a cycloalkenyloid-d ring, with the proviso that the cycloalkyl ring (dd) or the cycloalkenyloid-d ring) are not aromatic; and wherein the alkyl (dC? 2), alkenyl (C2-C? 2), alkynyl (C2-C? 2), the cycloalkyl ring (C4-Cs) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyl (CrC6); aril; heterocycloalkyloid-d); heteroaryl (C2-d); aryl (alkyl d-d) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkox d-d); aryl (d-alkoxy) -; acyl (d-Ce); alkylamine (CrCe) -; aryl (alkylamino d-d) -; aminoalkyl (CrCe) -; alkoxy (CrCe) -CO-NH-; alkylamino (CrCe) -CO-; alkenyl (C2-d); alkynyl (C2-Ce); hydroxyalkyl (CrCe) -; (CrdCalkyl alkoxy CrCe) -; (acyloxy CrCe) (alkyl d-Ce) -; nitro; cyanoalkyl (Crd) -; haloalkyl (CrCe) -; nitroalkyl (CrCe) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (CrCe) -; (acylamino d-dXalkyl d-Ce) -; (alkoxy CrCe) (acylamino d-d) -; aminoacyl (CrCe) -; (aminoacyl CrCe) (alkyl -Ce) -; (alkylamino Crd) (acyl CrCe) -; (alkyl Crd ^ aminoacylCrd) -; -CO2R2; alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R20N =; R2ON = alkyl (d-C6) -; R2ON = CR2 (alkyl dC6) -; -NR2 (OR2); -alkyl (CrC6) -NR2 (OR2); -C (0) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (Crd), aryl or aryl (d-Ce alkyl) -; R3C (0) 0-, and R3 is alkyl (CrCe), aryl or aryl (d-C6 alkyl) -; R 3 C (0) O-alkyl (CrC 6) -; R4R5N-C (O) -O-; R4-R5NS (0) 2- R4R5NS (0) 2 (alkyl d-C6) -; R4S (0) 2R5N-; R5S (0) 2R5N (alkyl dCe) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (C C 6); -C (= NR6) (N (R4) 2); -alkyl (CrC6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (alkyl d-d); -NH (alkyl d-Cß); aryl (alkyl d-d) -HN-; and a ketal; which comprises reacting a compound of formula (2) (2) with a compound of formula (3) (3) wherein X and Y are as defined above, in the presence of a base to form the compound of formula (4).

20. A process for preparing a compound of formula I (a) Ka) wherein X and Y are each independently selected from hydrogen, alkyl (d-Ci2), alkenyl (C2-C2), alkynyl (C2-Ci2), or X and Y are taken together with the carbon at which are joined to form a cycloalkyl ring (C4-Cs) or a cycloalkenyl ring (C5-d), with the proviso that the cycloalkyloid-d ring or the cycloalkenyloid-d ring are not aromatic; and wherein the alkyl (dC? 2), (C2-C? 2) alkenyl, (C2-C? 2) alkynyl, the cycloalkyloid-d ring or the cycloalkenyloid-d ring) are optionally substituted with one to three Z groups independently selected, and Z is selected from the group consisting of cyano; halo; alkyloid-d); aril; heterocycloalkylid-Cg); heteroaryl (C2-Cg); aryl (alkyl d-d) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (d-Ce); aryl (d-alkoxy); acyl (CrCe); alkylaminoCrd) -; aryl (alkylamino d-d) -; aminoalkyl (CrC6) -; alkoxy (CrC6) -CO-NH-; alkylamine (CrC6) -CO-; alkenyl (C2-d); alkynyl (C2-Ce); hydroxyalkyl (CrCe) -; (alkoxy CrCe) (alkyl d-d) -; (acyloxy d-Ce) (alkyl d-d) -; nitro; cyanoalkyl (CrCe) -; haloalkyl (d-Ce) -; nitroalkyl (CrCe) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (CrCe) -; (acylamino CrCe) (alkyl d-d) -; (alkoxy d-d) (acylamino d-d); aminoacyl (CrCe) -; (aminoacyl d-d) (Crd alkyl) -; (alkylamino CrCe) (acyl CrCe) -; (Cr ^ aminoacyloyl CrCe alkyl) -; -CO2R2; -alkyl (CrC6) -C? 2R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (CrC6 alkyl) -; -NR2 (OR2); -alkyl (C? -C6) -NR2 (OR2); -C (0) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (Crd), aryl or aryl (C6 alkyl) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R 3 C (0) 0-alkyl (d-Ce) -; R4R5N-C (0) -0-; R4R5NS (0) 2- R4R5NS (O) 2 (C6 alkyl) -; R4S (O) 2R5N-; R4S (0) 2R5N (alkyl d-d) -; m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (CrCe); -C (= NR6) (N (R4) 2); -alkyl (C? -C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; - OC (0) aryl (d-C6 alkyl); -NH (alkyl d-C6); aryl (d-C6 alkyl) -NH-; and a ketal; comprising: (a) reacting a compound of formula (5) or (5 ') (5) (5 ') wherein Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form the compound of formula (6); Y (6) (b) when W is H, reducing the compound of formula (6) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, reduce the compound of formula (6) formed in this manner and remove the protecting group, to form the compound of formula I (a).

21. A process for preparing a compound of formula l (a) Ka) wherein W and Y are each independently selected from hydrogen, alkyl (CrCi2), alkenyl (C2-Ci2), alkynyl (C2-C? 2), or X and Y are taken together with the carbon to which they are attached to forming a cycloalkyl ring (C4-Cs) or a cycloalkyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (C-C8) or the cycloalkenyl ring (C5-C8) are not aromatic; and wherein the alkyl (CrC2), alkenyl (C2-Ci2), alkynyl (C2-C2), the cycloalkyloid-d ring or the cycloalkenyl ring (C5-Cs) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyloid-d); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-Cg); aryl (CrCe alkyl) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (Crd); aryl (d-alkoxy) -; acyl (Crd); alkylamino (CrCe) -; aryl (alkylamino CrCe) -; aminoalkyl (CrCe) -; alkoxy (Crd) -CO-NH-; alkylamino (CrC6) -CO-; alkenyl (C2-Ce); alkynyl (C2-Ce); hydroxyalkyl (CrCe) -; (alkoxy d-d) (alkyl CrCe) -; (acyloxy d-d) (alkyl d-d) -; nitro; cyanoalkyl (Crd) -; haloalkyl (CrCe) -; nitroalkyl (CrCe) -; trifluoromethyl; trifluoromethyl (d-Cß alkyl) -; acylamino (CrCe) -; (acylamino d-d) (alkyl d-d) -; (alkoxy d-d) (acylamino Crd) -; aminoacyl (CrCe) -; (aminoacyl d-d) (Crd alkyl) -; (alkylamino d-dXacyl d-d) -; (alkyl Crd ^ aminoacylCrd) -; -CO2R .2.; -alkyl (CrC6) -C? 2R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (C6 alkyl) -; -NR2 (OR2); -alkyl (d-Ce) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (C? -C6) -C (0) (NR2OR2); -S (0) mR2: and each R2 is independently selected from nitrogen, alkyl (Crd), aryl or aryl (C6 alkyl) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R 3 C (0) 0-alkyl (CrC 6) -; R4R5N-C (0) -0-; R4-R5NS (0) 2- R4R5NS (0) 2 (alkyl d-C6) -; R4S (0) 2R5N-; R 4 S (0) 2 R 5 N (C 6 alkyl) -; and m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (CrC6); -C (= NR6) (N (R4) 2); -alkyl (CrC6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (d-C6 alkyl); -NH (alkyl d-d); aryl (CrC6 alkyl) -HN-; and a ketal; comprising: (a) reacting a compound of formula (5) or (5 ') (5) (5 ') in which Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form the compound of formula (7); Y (7) (b) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, hydrogenating the compound of formula (7) formed in this manner and removing the protecting group, to form the compound of formula "(a) 22.- A process for preparing a compound of formula l (a).

Ka) wherein X and Y are each independently selected from hydrogen, alkyl (dC? 2), alkenyl (C2-Ci2), alkynyl (C2-Ci2), or X and Y are taken together with the carbon to which they are attached to forming a cycloalkyl ring (C4-d) or a cycloalkenyl ring (C5-d), with the proviso that the cycloalkyl ring (C4-d) or the cycloalkenyloid-d ring) are not aromatic; and wherein the alkyl (C Ci 2), alkenyl (d-Ci 2), alkynyl (C 2 -C 2), the cycloalkyl ring (C 4 -d) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyl (Crd); aril; heterocycloalkyl (C2-Cg); heteroaryl (d-Cg); aryl (alkyl d-d) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (Crd); aryl (alkoxy-Ce) -; aci (d-d); alkylamino (CrCe) -; aryl (alkylamino d-Ce) -; aminoalkyl (CrCe) -; alkoxy (CrC6) -CO-NH-; alkylamino (CrCe) -CO-; alkenyl (C2-Ce); alkynyl (C2-Ce); hydroxyalkyl (CrCe) -; (alkoxy d-d) (alkyl CrCe) -; (acyloxy d-d) (alkyl d-Ce) -; nitro; cyanoalkyl (CrCe) -; haloalkyl (CrCe) -; nitroalkyl (CrC6) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (CrCe) -; (acylamino d-d) (alkyl CrCe) -; (alkoxy CrCe) (acylamino CrCe) -; aminoacylid-d) -; (aminoacyl CrCe) (alkyl d-d) - (alkylamino d-d) (acyl d-d) -; (alkyl Crd ^ aminoacylCrd) -; -CO2R2-alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON = R2ON = alkyl (CrC6) -; R2ON = CR2 (C? -C? Alkyl) -; -NR2 (OR2); -alkyl (Crd) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from nitrogen, alkyl (CrCe), aryl or aryl (CrC6 alkyl) -; R3C (0) 0-, and R3 is alkyloid-d), aryl or aryl (d-C6 alkyl) -; R 3 C (O) 0-alkyl (CrC 6) -; R4R5N-C (0) -0-; R 4 -R 5 NS (0) 2-R R 5 NS (0) 2 (C 1 -C 6 alkyl) -; R4S (0) 2R5N-; R 4 S (0) 2 R 5 N (C C β alkyl) -; and m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (d-C6); -C (= NR6) (N (R4) 2); -alkyl (d-C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; - OC (0) aryl (alkyl d-d); -NH (CrC6 alkyl); aryl (CrC6 alkyl) -HN-; and a ketal; comprising: (a) reacting a compound of formula (5) or (5 ') (5) (5 ') in which Q is halogen, W is hydrogen or a protective group, and X and Y they are as defined above, with a base to form the compound of formula (6); (6) (b) reacting the compound of formula (6) formed in this manner with a base, to form a compound of formula (7); Y (7) (c) when W is H, hydrogenating the compound of formula (7) in this manner, to form the compound of formula I (a); or (d) when W is a protecting group, hydrogenating the compound of formula (7) formed in this manner and removing the protecting group, to form the compound of formula I (a).

23.- A process for preparing a compound of formula I (a) Ka) wherein X and Y are each independently selected from hydrogen, alkyl (CrC? 2), alkenyl (C2-Ci2), alkynyl (CrC? 2), or X and Y are taken together with the carbon to which they are attached to forming a cycloalkyl ring (C4-Cs) or a cycloalkenyl ring (C5-d), provided that the cycloalkyl ring (dd) or the cycloalkyl ring (C5-d) are not aromatic; and wherein the alkyl (CrC? 2), alkenyl (d-Ci2), alkynyl (C2-Ci2), the cycloalkyloid-d ring), or the cycloalkenyl ring (dd) are optionally substituted with one to three groups Z independently selected, and Z is selected from the group consisting of cyano; halo; alkyl (Crd); aril; heterocycloalkyl (d-Cg) heteroaryl (C2-C9); aryl (alkyl (Crd) -; = 0; = CHO (alkyl (Crd); amino; hydroxy; alkoxy (Crd); aryl (alkoxy); acyl (Crd); alkylamino (Crd) -; alkylamino Crd) -; aminoalkyl (dd) -; alkoxy (Crd) -CO-NH-; alkylamino (d-C6) -CO-; alkenyl (C2-d); alkynyl (C2-C6) hydroxyalkyl (Crd) -; (alkoxy dd) (alkyl dd) -; (acyloxy dd) (CrC6 alkyl) -; nitro; cyanoalkyl (CrCe) -; haloalkyl (Crd) -; n-alkyl (Crd) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (CrCe) -; (acylamino d-d) (CrCe alkyl) -; (alkoxy d-d) (acylamino d-d) -; aminoacyl (CrCe) -; (aminoacrylic CrC6) (alkyl CrCe) -; (alkylamino d-d) (acyl d-d) -; (alkyl CrCe) 2-aminoacyl (CrCe) -; -CO2R2; -alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2 =; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (Ci-Ce alkyl) -; -NR2 (OR2); -alkyl (CrC6) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (d-C6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (d-d), aryl or aryl (d-d alkyl) -; R3C (0) 0-, and R3 is alkyl (d-d), aryl or aryl (d-C6 alkyl) -; R 3 C (0) O-alkyl (CrC 6) -; R4R5N-C (0) -0-; R4-R5NS (0) 2- R4R5NS (0) 2- (alkyl d-Ce) -; R4S (0) 2R5N-; R 4 S (0) 2 R 5 N (C C 6 alkyl) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (d-Ce); -C (= NR6) (N (R) 2); -alkyl (d-C6) -C (= NR6) (N (R) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (alkyl d-d) -; NH (alkyl d-d); aryl (d-C6 alkyl) -HN-; and a ketal; comprising: (a) reacting a compound of the formula of (5) or (5) (5 ') in which Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form the compound of formula (6); (6) (b) reacting the compound of formula (6) formed in this manner with a base, to form a compound of formula (7); Y (7) (c) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (d) when W is a protecting group, removing the protecting group of the compound of formula (7) formed in this manner, to form the compound of formula I (b) Kb) and hydrogenate the compound of formula I (b) formed in this manner, to form the compound of formula I (a).

24. A process for preparing a compound of formula I (a) Ka) in which X and Y are each independently selected from hydrogen, alkyl (CrC 2), alkenyl (C 2 -Ci 2), alkynyl (C 2 -C 12), or X and Y are taken together with the carbon to which they are attached. joined to form a cycloalkyl ring (C4-d) or a cycloalkenyloid-d ring, with the proviso that the cycloalkyl ring (C4-d) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and wherein the alkyl (d-Ci2), alkenyl (C2-Ci2), alkynyl (C2-Ci2), the cycloalkyl ring (C4-d) or the cycloalkenyl ring (dd) are optionally substituted with one to three Z groups independently selected, and Z is selected from the group consisting of cyano; halo; alkyl (Crd); aril; heterocycloalkyl-d); heteroaryloid-d); aryl (a-d-d alkyl) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (Crd); aryl (alkoxy d-d) -; acyl (Crd); alkylaminoCrd) -; aryl (alkylamino -d) -; aminoalkyl (CrCe) -; alkoxy (d-C6) -CO-NH-; alkylamino (CrC6) -CO-; alkenyl (C2-d); alkynyl (CrC6); hydroxyalkyl (CrCe) -; (CrC6 alkoxy) (d-d alkyl) -; (acyloxy d-d) (alkyl d-d) -; nitro; cyanoalkyl (CrC6) -; haloalkyl (CrC6) -; nitroalkyl (CrC6) -; trifluoromethyl; trifluoromethyl (alkyl dCe) -; acylamino (d-d) -; (acylamino d-d) (alkyl d-d) -; (alkoxy d-d) (acylamino d-d) -; aminoacyl (CrCe) -; (C6-C6 aminoacyl) (d-d alkyl) -; (alkylamino d-d) (acyl d-d) -; (alkyl CrCe) 2 aminoacyl (CrCe) -; -C02R2; -alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (alkyD-Cß) -; NR2 (OR2); -alkyl (Crd) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (CrCe), aryl or aryl (CrC6 alkyl) -; R 3 C (0) 0-, and R 3 is alkyl (CrC 6), aryl or aryl (d-d alkyl) -; R3C (0) O-alkyl (CrCe) -; R4R5N-C (0) -0-; R4-R5NS (0) 2- R4R5NS (0) 2- (Ci-Ce alkyl) -; R4S (0) 2R5N-; R4S (O) 2R5N (Ci-Ce alkyl) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (d-d); -C (= NR6) (N (R) 2); -alkyl (CrC6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2, is as defined above; -OC (0) aryl (alkyl d-d); -NH (CrC6 alkyl); aryl (d-C6 alkyl) -HN-; and a ketal; comprising: (a) reacting a compound of formula (5) or (5 ') (5) (5 ') in which Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form the compound of formula (7); Y (7) (b) when W is H, hydrogenating the compound of formula (7) formed in this manner, to form the compound of formula I (a); or (c) when W is a protecting group, removing the protecting group of the compound of formula (7) thereby forming, to form the compound of formula I (b) Kb) and hydrogenating the compound of formula I (b) to thereby form the compound of formula I (a).

25. A process for preparing a compound of formula I (b) Kb) in which X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, or X and Y are taken together with the carbon to which they are attached. joined to form a cycloalkyl ring (dd) or a cycloalkenyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (dd) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and wherein the (C1-C12) alkyl, (C2-C12) alkenyl, alkynyl (d-C12), the cycloalkyl ring (dd) or the cycloalkenyl ring (dd) are optionally substituted with one to three independently selected Z groups , and Z is selected from the group consisting of cyano; halo; alkyl (d-d); aril; heterocycloalkyl (d-d); heteroaryl (C2-C9); aryl (alkyl (dd) -; = 0; = CHO (alkyl dd); amino; hydroxy; alkoxy (dd); aryl (alkoxy CrCe) -; acyl (dd); alkylamino (dd); aryl (alkylamino dd) - aminoalkyl (CrCe) -; alkoxy (dd) -CO-NH; alkylamino (C? -d) -CO-; alkenyl (dd); alkynyl (dd); hydroxyalkyl (dd) -; (alkoxy Crd) (alkyl); (CrCe) -; (acyloxy Crd) (alkyl (CrCe) -; nitro; cyanoalkyl (dd) -; haloalkyl (-d) -; nitroalkyl (dd) -; trifluoromethyl; trifluoromethyl (alkyl dd) -; acylamino (dd) ) -; (acylamino dd) (alkyl dd) -; (CrdXacylamino alkoxy CrCe) -; aminoacyl (Crd) -; (aminoacyl dd) (alkyl dd); (alkylamino CrCe) (acyl dCe) -; d-dfeaminoacyl (dd) -; -CO2R2; -alkyl (Crd) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; = alkyl (d-C6) -; R2ON = CR2 (alkyl d-C6) -; -NR2 (OR2); -alkyl (d-C6) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (d-C6) -C (O) (NR2OR2); -S (O) mR2; and each R2 is independently selected from hydrogen, alkyl (dd), aryl or aryl (d-C6 alkyl) -; R3C (0) 0-, and R3 is a alkyl (CrC6), aryl or aryl (alkyl d-d) -; R 3 C (0) 0-alkyl (CrCe) -; R4R5N-C (0) -O-; R4-R5NS (O) 2- R4R5NS (O) 2 (Crd alkyl) -; R4S (0) 2R5N-; R4S (0) 2R5N (alkyl d-d) -; and m is O, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (d-d); -C (= NR6) (N (R4) 2); -alkyl (C? -C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above, -OC (0) aryl (CrCe alkyl); -NH (CrCe alkyl); aryl (alkyl (CrCe) -HN-; and a ketal comprising: (a) reacting a compound of formula (5) or (5 ') wherein Q ^ s halogen, W is hydrogen g_, a protective group, and X and Y are as defined above, with a base to form the compound of formula (6); (b) reacting the (6) formed in this manner with a base, to form a compound of formula I (b) when W is H, and a compound of formula (7) when W is a protecting group; Y (7) (c) when W is a protecting group, remove the protecting group of the compound of formula (7) formed in this manner, to form the compound of formula I (b).

26. - A process for preparing a compound of formula I (b) Kb) in which X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, or X and Y are taken together with the carbon to which they are attached. joined to form a cycloalkyl ring (dd) or a cycloalkenyl ring (dd), with the proviso that the cycloalkyl ring (dd) or the cycloalkenyl ring (Cs-Ce) are not aromatic; and wherein the (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C2) alkynyl, the cycloalkyl ring (dd) or the cycloalkenyl ring (dd) are optionally substituted with one to three Z groups independently selected, and Z is selected from the group consisting of cyano; halo; alkyl (CrCe); aril; heterocycloalkyl (C2-Cg); heteroaryl (d-d); aryl (alkyl d-d) -; = 0; = CHO (CrCe alkyl); Not me; hydroxy; alkoxy (d-d); aryl (d-alkoxy); acyl (d-d); alkylamino (d-d) -; aryl (alkylamino Crd) -; aminoalkyl (d-d) -; alkoxy (Crd) -CO-NH; alkylamino (C? -C6) -CO; alkenyl (d-d); (C2-C6) alkynyl; hydroxyalkyl (d-d) -; (alkoxy-d) (alkyl (CrCe) -; (acyloxy d-d) (alkyl (CrCe) -; nitro; cyanoalkyl (Crd) -; haloalkyl (d-d) -; nitroalkyl (CrCe) -; trifluoromethyl; trifluoromethyl (alkyl) d-d) -; acylamino (Crd) -; (acylamino d-d) (alkyl d-d) -; (alkoxy d-d) (acylamino d-d) -; aminoacyl (d-Ce) -; (aminoacyl d-d) (alkyl d-d) -; (alkylamino d-d) (acyl d-d); (alkyl dd ^ aminoacyl (dd) -; -CO2R2; -alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (Ci-Ce) -; R2ON = CR2 (d-C6 alkyl) -; -NR2 (OR2), -alkyl (d-C6) -NR2 (OR2); -C (O) (NR2OR2), -alkyl (d-C6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (dd), aryl or aryl (alkyl (d-d) -; R3C (O) 0-, and R3 is alkyl (d-d), aryl or aryl (alkyl d-d) -; R 3 C (O) O-alkyl (d-d) -; R4R5N-C (0) -0-; R4-R5NS (0) 2-R4R5NS (0) 2 (alkyl d-C6) -; R4S (0) 2R5N-; R4S (0) 2R5N (Ci-Ce alkyl) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (d-d); -C (= NR6) (N (R4) 2); -alkyl (d-C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; - OC (0) aryl (alkyl d-d); -NH (Ci-Ce alkyl); aryl (d-C6 alkyl) -HN-; and a ketal; who understands; (a) reacting a compound of formula (5) or (5 ') (5) (5 ') in which Q is halogen, W is hydrogen or a protecting group, and X and Y are as defined above, with a base pair forming the compound of formula I (b) when W is H, and a compound of formula (7) when W is a protecting group; Y (7) (b) when W is a protecting group, remove the protecting group of the compound of formula (7) formed in this manner, to form the compound of formula I (b).

27. The process of claim 1, wherein X and Y are taken together with the carbon to which they are attached to form a cycloalkyl ring (d-d) or a cycloalkenyl ring (Cs-Cs) which is optionally substituted.

28. The process of claim 27, wherein the cycloalkyl ring (d-d) or the cycloalkenyl ring (d-d) is substituted with one to three independently selected Z groups.

29. The process of claim 27, wherein X and Y are taken together with the carbon to which they are attached to form a cyclohexyl or cyclohexenyl ring.

30. The process of claim 27, wherein X and Y are taken together with the carbon to which they are attached to form a cyclopentyl or cyclopentenyl ring.

31. - The process of claim 27, wherein the ring cycloalkyl (d-d) or the cycloalkenyl ring (Cs-Cs) is unsubstituted.

32. The process of claim 27, in which the ring cycloalkyl (d-d) or the cycloalkenyl ring (Cs-Cs) is monosubstituted.

33. The process of claim 27, wherein the cycloalkyl ring (d-d) or the cycloalkenyl ring (Cs-Cs) is disubstituted.

34. The process of claim 29, wherein the cyclohexyl or cyclohexenyl ring is monosubstituted in the 3 or 4 position.

35. - The process of claim 30, wherein the ring Cyclopentyl or cyclopentenyl is monosubstituted in the 3-position.

36. - A compound that has the structure of formula (4) (4) wherein W is hydrogen or a protecting group; and wherein X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-C2) alkenyl, (C2-C2) alkynyl, or X and Y are taken together with carbon to which they are attached to form a cycloalkyl ring (dd) or a cycloalkenyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (d-Cg) or the cycloalkenyl ring (Cs-Cs) are not aromatic; and in which the alkyl (C? -C-? 2), (C2-C12) alkenyl, (C2-C12) alkynyl, the cycloalkyl ring (d-Cs) or the cycloalkenyl ring (dd) are optionally substituted with one to three independently selected Z groups , and Z is selected from the group consisting of cyano; halo; alkyl (CrCe); aril; heterocycloalkyl (d-d); heteroaryl (d-d); aryl (alkyl (dd) -; = 0; = CHO (alkyl CrCe); amino; hydroxy; alkoxy (CrCe); aryl (alkoxy CrCe) -; acyl (dd); alkylamino (CrCe) -; aryl (alkylamino) dd) - aminoalkyl (dd) -; alkoxy (d-d) -CO-NH-; alkylamino (CrCe) -CO-; alkenyl (d-d); (C2-C6) alkynyl; hydroxyalkyl (d-d) -; (alkoxy d-CβXalkyl CrCe) -; (acyloxy d-dXalkyl d-d) -; nitro; cyanoalkyl (CrCe) -; haloalkyl (d-d) -; nitroalkyl (d-d) -; trifluoromethyl; trifluoromethyl (alkyl CrCe) -; acylamino (d-d) -; (acylamino Crd) (alkyl d-d) -; (alkoxy d-dXacylamino d-Ce) -; aminoacyl (CrCe) -; (aminoacyl d-Ce) (alkyl d-d) -; (alkylamino C? -Ce) (acyl CrCe) -; (alkyl d-C6) 2-aminoacyl (CrC6) -; -C02R2; -alkyl (Crd) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (d-C6) -; R2ON = CR2 (d-C6 alkyl) -; - NR2 (OR2); -alkyl (C? -C6) -NR2 (OR2); -C (0) (NR2OR2); -alkyl (d-d) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (d-d), aryl or aryl (d-d alkyl) -; R3C (0) 0-, and R3 is alkyl (dd), aryl or aryl (alkyl (dd) -; R3C (0) 0-alkyl (CrC6) -; R4R5N-C (O) -0-; R4-R5NS (0) 2- R4R5NS (O) 2 (Ci-Ce alkyl) -; R4S (O) 2R5N-; R4S (0) 2R5N (dd alkyl) -; and m is 0, 1 or 2, and R4 and R5 are selected each independently from hydrogen or alkyl (dd); -C (= NR6) (N (R4) 2); -alkyl (CrC6) -C (= NR6) (N (R) 2), and R6 represents OR2 or R2 , and R 2 is as defined above: -OC (0) aryl (dd alkyl) -NH (Crd alkyl), aryl (dd alkyl) -HN-, and a ketal.

37. - The compound of claim 36, having the structure of formula (4a), wherein W is as defined above and n is 0, 1, 2 or 3.

38.- The compound of claim 37, having the structure of formula (4b) or (4c), in which W is as defined above.

39.- The compound of claim 36, having the structure of the formula (4d), wherein W and Z are as defined above, and in which n is 0, 1, 2 or 3.

40. - The compound of claim 39, having the structure of formula (4e) or (4f), in which W and Z are as defined above.

41.- The compound of claim 36, having the structure of the formula (4g), wherein W and Z are as defined above, and wherein n is 0, 1, 2 or 3.

42.- The compound of claim 41, having the structure of the formula (4h) or (4i) , in which W and Z are as defined above.

43.- A compound that has the structure of formula (5), (5) in which Q is halogen; in which W is hydrogen or a protecting group; and in wherein X and Y are each independently selected from hydrogen, (C 1 -C 12) alkyl, (C 2 -C 12) alkenyl, (C 2 -C 12) alkynyl, or X and Y are taken together with the carbon to which they are attached to form a ring cycloalkyl (d-d) or a cycloalkenyl ring (Cs-Cs), with the proviso that the cycloalkyl ring (d-d) or the cycloalkenyl ring (d-d) are not aromatics; and wherein alkyl (C1-C12), alkenyl (dC-12), alkynyl (C2-C12), the cycloalkyl ring (dd) or the cycloalkenyl ring (Cs-Cs) are optionally substituted with one to three selected Z groups independently, and Z is selected from the group consisting of cyano; halo; alkyl (d-d); aril; heterocycloalkyl (d-d); heteroaryl (C2-Cg); aril d-d) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (d-d); aryl (d-alkoxy) -; acyl (d-d); alkylamino (d-d) -; aryl (alkylamino CrCe) -; aminoalkyl (d-Cß) -; alkoxy (d-Ce) -CO-NH-; alkylamino (d-Cß) -CO-; alkenyl (C2-C6); alkynyl (C2-d); hydroxyalkyl (d-d) -; (alkoxy d-dXalkyl d-d) -; (Crd alkoxy) (alkyl (Crd) -; nitro; cyanoalkyl (Crd) -; haloalkyl (Crd) -; nitroalkyl (Crd) -; trifluoromethyl; trifluoromethylCrd alkyl) -; acylamino (Cr d) -; (acylamino d-d) (alkyl d-d) -; (alkoxy d-d) (acylamino Crd) -; aminoacylid-d) -; (aminoacyl d-d) (alkyl d-d) -; (alkylamino d-d) (C6-C6 acyl) -; (alkyl d-dkaminoacylCrd) -; -C02R2; -alkyl (Crd) -C02R2; -C (0) N (R2) 2; -alkyl (CrC6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (d-C6) -; R2ON = CR2 (alkyl dC6) -; -NR2 (OR2); -alkY (Crd) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (CrC6) -C (0) (NR2OR2); -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (Crd), aryl or aryl (d-C6 alkyl) -; R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (C6 alkyl) -; R3C (0) 0-alkyl (C? -Ce) -; R4R5N-C (0) -0-; R4-R5NS (0) 2- R4R5NS (0) 2 (Ci-Ce alkyl) -; R4S (0) 2R5N-; R 4 S (0) 2 R 5 N (C 6 alkyl) -; and m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or alkyl (Crd); -C (= NR6) (N (R4) 2); -alkyl (C? -C6) -C (= NR6) (N (R4) 2), and R6 represents OR2 or R2, and R2 is as defined above; -OC (0) aryl (CrCe alkyl); -NH (alkyl d-d); aryl (CrCß alkyl) -HN-; and a ketal.

44.- The compound of claim 43, having the structure of the formula (5 a), wherein Q and W are as defined above, and n is 0, 1, 2 or 3.

45.- the compound of claim 44, having the structure of formula (5b) or (5c), in which Q and W are as defined above.

46.- The compound of claim 43, having the structure of the formula (5d), wherein Q, W and Z are as defined above, and n is 0, 1, 2 or 3.

47.- The compound of claim 46, having the structure of formula (5e) or (5f), in which Q, W and Z are as defined above.

48. - The compound of claim 43, having the structure of the formula (5g), wherein Q, W and Z are as defined above, and n is 0, 1, 2 or 3.

49.- The compound of claim 48, having the structure of the formula (5h) or (5i), in which Q, W and Z are as defined above.

50.- The compound of claim 43, wherein Q is bromine, iodine or chlorine.

51.- The compound of claim 43, wherein Q is bromine.

52. A compound having the structure of formula (5 '), in which Q is halogen; and wherein X and Y are each independently selected from hydrogen, (C1-C12) alkyl, (C2-Ci2) alkenyl, (C2-C2) alkynyl, or X and Y are taken together with the carbon to which they are attached to form a cycloalkyl ring (d-Cs) or a cycloalkenyl ring (C5-d), with the proviso that the cycloalkyl ring (d-Cs) or the cycloalkenyloid-d ring are not aromatic; and wherein the alkyl (C? C? 2), (C2-C? 2) alkenyl, (C2-C? 2) alkynyl, the cycloalkyl ring (C4-d) or the cycloalkenyloid-d ring) are optionally substituted with one to three independently selected Z groups, and Z is selected from the group consisting of cyano; halo; alkyl (Crd); aril; heterocycloalkyl (C2-Cg); heteroaryl (C2-Cg); aryl (alkyl d-d) -; = 0; = CHO (alkyl d-d); Not me; hydroxy; alkoxy (d-d); aryl (d-alkoxy) -; aci (d-Ce); alkylamino (CrCe) -; aryl (alkylamine d-d) -; aminoalkyl (CrC6) -; alkoxy (CrC6) -CO-NH-; alkylamine (CrC6) - CO-; alkenyl (d-d); (C2-C6) alkynyl; hydroxyalkyl (CrCe) -; (CrC6 alkoxy) (d-d alkyl) -; (acyloxy d-d) (alkyl d-d) -; nitro; cyanoalkyl (CrCe) -; haloalkyl (CrC6) -; nitroalkyl (CrC6) -; trifluoromethyl; trifluoromethyl (alkyl d-d) -; acylamino (Crd) -; (acylamino d-d) (CrC6 alkyl) -; (CrC6 alkoxy) (acylamino CrCe) -; amnoacyl (CrCe) -; (aminoacyl d-d) (CrCe alkyl) -; (alkylamino d-d) (acyl CrC6) -; (alkyl CrCe) 2 aminoacryl (CrCe) -; -CO2R2; -alkyl (CrC6) -C02R2; -C (0) N (R2) 2; -alkyl (C? -C6) -C (0) N (R2) 2; R2ON =; R2ON = alkyl (CrC6) -; R2ON = CR2 (CrC6 alkyl) -; -NR2 (OR2); -alkyl (d-Ce) -NR2 (OR2); -C (O) (NR2OR2); -alkyl (d-C6) -C (0) (NR2OR2; -S (0) mR2; and each R2 is independently selected from hydrogen, alkyl (Crd), aryl or aryl (d-C6 alkyl) - R3C (0) 0-, and R3 is alkyl (CrC6), aryl or aryl (d-C6 alkyl) -; R3C (0) 0-alkyl (Crd) -; R4R5N-C (0) -0-; R -R5NS (0) 2- R4R5NS (0) 2 (alkyl d-Ce) -; R4S (O) 2R5N-; RS (0) 2R5N (alkyl dC6) -; and m is 0, 1 or 2, and R4 and R5 are each independently selected from hydrogen or alkyl (d-C6); -C (= NR6) (N (R4) 2); -alkyl (C? -C6) -C (= NR6) (N ( R) 2), and R6 represents OR2 or R2, and R2 is as defined above: -OC (0) aryl (Ci-Ce alkyl); -NH (d-C6 alkyl); aryl (C? -C6 alkyl); -HN-, and a ketal.